Variant 9-128285952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001318089.2(SWI5):c.247G>A(p.Asp83Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SWI5
NM_001318089.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.90

Variant links:

Genes affected

SWI5 (HGNC:31412): (SWI5 homologous recombination repair protein) Involved in cellular response to ionizing radiation and double-strand break repair via homologous recombination. Part of Swi5-Sfr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

SWI5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18089989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SWI5	NM_001318089.2 linkuse as main transcript	c.247G>A	p.Asp83Asn	missense_variant	4/5	ENST00000418976.3	NP_001305018.2	Q1ZZU3
SWI5	NM_001379267.1 linkuse as main transcript	c.394G>A	p.Asp132Asn	missense_variant	4/5		NP_001366196.1
SWI5	NM_001040011.2 linkuse as main transcript	c.367G>A	p.Asp123Asn	missense_variant	4/5		NP_001035100.2	Q1ZZU3
SWI5	NM_001318092.2 linkuse as main transcript	c.274G>A	p.Asp92Asn	missense_variant	4/5		NP_001305021.1	Q1ZZU3H7C5E9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SWI5	ENST00000418976.3 linkuse as main transcript	c.247G>A	p.Asp83Asn	missense_variant	4/5	2	NM_001318089.2	ENSP00000411469.3		H7C3F2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.562G>A (p.D188N) alteration is located in exon 4 (coding exon 4) of the SWI5 gene. This alteration results from a G to A substitution at nucleotide position 562, causing the aspartic acid (D) at amino acid position 188 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;T;T;T;.

Eigen

Benign

0.025

Eigen_PC

Benign

0.069

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.18

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

.;M;.;.;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

.;N;.;.;.

REVEL

Benign

0.056

Sift

Uncertain

0.018

.;D;.;.;.

Sift4G

Benign

0.25

T;D;T;T;T

Polyphen

0.98

.;D;.;.;.

Vest4

0.30

MutPred

0.41

.;Gain of phosphorylation at Y185 (P = 0.0986);.;.;.;

MVP

0.16

MPC

0.64

ClinPred

0.89

GERP RS

2.6

Varity_R

0.081

gMVP

0.097

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over